@article{APS9441,
author = {Byung-Wook KIM and Sandeep Vasant MORE and Yo-Sep YUN and Hyun-Myung KO and Jae-Hwan KWAK and Heesoon LEE and Kyoungho SUK and In-Su KIM and Dong-Kug CHOI},
title = {A novel synthetic compound MCAP suppresses LPSinduced murine microglial activation in vitro via inhibiting NF-kB and p38 MAPK pathways},
journal = {Acta Pharmacologica Sinica},
volume = {37},
number = {3},
year = {2017},
keywords = {},
abstract = {Aim: To investigate the anti-neuroinflammatory activity of a novel synthetic compound, 7-methylchroman-2-carboxylic acid N-(2- trifluoromethyl) phenylamide (MCAP) against LPS-induced microglial activation in vitro.
Methods: Primary mouse microglia and BV2 microglia cells were exposed to LPS (50 or 100 ng/mL). The expression of iNOS and COX-2, proinflammatory cytokines, NF-κB and p38 MAPK signaling molecules were analyzed by RT-PCR, Western blot and ELISA. The morphological changes of microglia and nuclear translocation of NF-ĸB were visualized using phase contrast and fluorescence microscopy, respectively.
Results: Pretreatment with MCAP (0.1, 1, 10 μmol/L) dose-dependently inhibited LPS-induced expression of iNOS and COX-2 in BV2 microglia cells. Similar results were obtained in primary microglia pretreated with MCAP (0.1, 0.5 μmol/L). MCAP dose-dependently abated LPS-induced release of TNF-α, IL-6 and IL-1β, and mitigated LPS-induced activation of NF-κB by reducing the phosphorylation of IκBα in BV2 microglia cells. Moreover, MCAP attenuated LPS-induced phosphorylation of p38 MAPK, whereas SB203580, a p38 MAPK inhibitor, significantly potentiated MCAP-caused inhibition on the expression of MEF-2 (a transcription factor downstream of p38 MAPK).
Conclusion: MCAP exerts anti-inflammatory effects in murine microglia in vitro by inhibiting the p38 MAPK and NF-κB signaling pathways and proinflammatory responses. MCAP may be developed as a novel agent for treating diseases involving activated microglial cells.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/9441}
}